Ethyl Acetate → HCID 90423010, compound

HRID 1050182Notes

Reaction equation

HRID 1050182 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27](O)=[O:28])=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2].[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]([F:46])([F:45])[C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:34]([C:47]([F:50])([F:49])[F:48])[CH:33]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CC(=O)OCC>N1C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([CH2:38][C:39]([F:45])([F:46])[C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:34]([C:47]([F:48])([F:49])[F:50])[CH:33]=3)=[O:28])=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl Acetate2×HCID 111923Propylphosphonic anhydrideHCID 904166242-(4-(5-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl) acetic acidHCID 90422687HCID 90422687, compound

Product 1

HCID 90423010HCID 90423010, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
20 °C

Procedure

To a mixture of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (150 mg, 0.365 mmol) in pyridine (2 mL) were added ethyl 3-(4-amino-2-(trifluoromethyl)phenyl)-2,2-difluoropropanoate (108 mg, 0.365 mmol) and T3P® (EA solvate) (464 mg, 0.729 mmol). The mixture was stirred at 20° C. for 1 h. LCMS and TLC (PE/EA=1:1, Rf=0.5) showed the reaction was finished. The mixture was concentrated and then purified by TLC (PE/EA=1:1, Rf=0.5) to give ethyl 3-(4-(2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamido)-2-(trifluoromethyl)phenyl)-2,2-difluoropropanoate (120 mg, 0.150 mmol, 41.2% yield): 1H NMR (400 MHz, CD3OD-d4) δ 8.08-8.02 (m, 1H), 7.94 (d, J=2.0 Hz, 1H), 7.78 (s, 1H), 7.54-7.33 (m, 7H), 6.90 (d, J=8.8 Hz, 2H), 5.35 (s, 2H), 4.26 (q, J=7.3 Hz, 2H), 4.13 (q, J=7.1 Hz, 2H), 3.81 (s, 2H), 3.78 (s, 3H), 3.63-3.52 (m, 2H), 1.41 (t, J=7.1 Hz, 3H), 1.25 (t, J=7.2 Hz, 3H); ES-LCMS m/z 691 (M+H).

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by TLC (PE/EA=1:1, Rf=0.5)

Sources & evidence

ORD record
ord-877013d75a5c45609233445867a9ca0b
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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